The Chinese hamster V79 cell mutant V-H4 is phenotypically like Fanconi anemia cells

Zdzienicka, M. Z.; Arwert, Fré; Neuteboom, I.; Rooimans, M.; Simons, J.W.I.M.

doi:10.1007/bf01233098

Cited by 29 publications

(18 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The only exception was the cell line V-H4. V-H4 and FA-A may represent the same molecular defect since there is evidence from cell fusion studies to indicate that FA-A and V-H4 cell lines belong to the same complementation group (52). It is also possible that the V-H4 gene product participates in a step of the repair reaction subsequent to DNA synthesis.…”

Section: Discussionmentioning

confidence: 99%

Interstrand Cross-Links Induce DNA Synthesis in Damaged and Undamaged Plasmids in Mammalian Cell Extracts

Peterson

et al. 1999

Molecular and Cellular Biology

View full text Add to dashboard Cite

Mammalian cell extracts have been shown to carry out damage-specific DNA repair synthesis induced by a variety of lesions, including those created by UV and cisplatin. Here, we show that a single psoralen interstrand cross-link induces DNA synthesis in both the damaged plasmid and a second homologous unmodified plasmid coincubated in the extract. The presence of the second plasmid strongly stimulates repair synthesis in the cross-linked plasmid. Heterologous DNAs also stimulate repair synthesis to variable extents. Psoralen monoadducts and double-strand breaks do not induce repair synthesis in the unmodified plasmid, indicating that such incorporation is specific to interstrand cross-links. This induced repair synthesis is consistent with previous evidence indicating a recombinational mode of repair for interstrand cross-links. DNA synthesis is compromised in extracts from mutants (deficient in ERCC1, XPF, XRCC2, and XRCC3) which are all sensitive to DNA cross-linking agents but is normal in extracts from mutants (XP-A, XP-C, and XP-G) which are much less sensitive. Extracts from Fanconi anemia cells exhibit an intermediate to wild-type level of activity dependent upon the complementation group. The DNA synthesis deficit in ERCC1-and XPF-deficient extracts is restored by addition of purified ERCC1-XPF heterodimer. This system provides a biochemical assay for investigating mechanisms of interstrand cross-link repair and should also facilitate the identification and functional characterization of cellular proteins involved in repair of these lesions.DNA interstrand cross-linking agents are among the oldest and yet still most effective anticancer drugs available in the clinic, and the chemotherapeutic use of the early forms of these chemicals, such as mustard gas and nitrogen mustard, extends back to before the Second World War. The alkylation chemistry of these drugs was also elucidated shortly after that war, and their cellular pharmacology was extensively studied during the 1970s and 1980s (27). In contemporary chemotherapy, interstrand cross-linking agents such as cyclophosamide, melphalan, and cisplatin are among the most potent antitumor agents. Despite this lengthy history of clinical use and pharmacologic investigation, the mechanisms of repair of the lesions produced in DNA by interstrand cross-linking agents have not been extensively studied. This situation of relative neglect of biochemical pathways of cross-link repair contrasts with the striking advances that have been accomplished in the past decade in other DNA damage processing pathways, such as nucleotide excision repair (NER), base excision repair, and mismatch repair (18).Current evidence (44) indicates that the error-free repair of both interstrand cross-links and double-strand breaks involves a recombinational mechanism in which an undamaged donor chromosome provides a homologous copy for the repair of the damaged template. Both of these lesions are highly deleterious, and it has been shown in certain yeast genetic backgrounds in which particul...

show abstract

Section: Discussionmentioning

confidence: 99%

Interstrand Cross-Links Induce DNA Synthesis in Damaged and Undamaged Plasmids in Mammalian Cell Extracts

Peterson

et al. 1999

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…We only considered differences of more than twofold as biologically meaningful. Using these criteria, we found that two mutant Chinese hamster cell lines showed a twoto threefold decrease in the level of microhomologydirected end-joining, V-H4 and CL-V5B [36][37][38] (Table 2). To make this difference more easily visible, we also used another transfection reagent (Lipofectin instead of SuperFect), which results in a much higher relative level of microhomology use in wild-type cells (Table 3 and Fig.…”

Section: Mutants Showing Decreased Microhomology Usementioning

confidence: 99%

Different types of V(D)J recombination and end-joining defects in DNA double-strand break repair mutant mammalian cells

et al. 2002

View full text Add to dashboard Cite

“…Genetic complementation analysis has shown that the Chinese hamster cell line V-H4, a mutant derived from the V79 cell line, belongs to the same complementation group as FA-A cells (Arwert et al, 1991). V-H4 cells are hypersensitive to many cross-linking agents such as MMC (30 fold more sensitive than the wild-type cells) (Zdzienicka et al, 1987) and exhibit an increased frequency of chromosomal breakage (Zdzienicka et al, 1990) and increased apoptosis (Papouli et al, 2000;Papouli et al, 2002) upon treatment with MMC. Since we previously demonstrated that V-H4 cells are not defective in the initial excision step of ICL repair (Larminat et al, 1998), this prompted us to study the efficiency of HR pathways in these cells.…”

Section: Introductionmentioning

confidence: 99%

Impairment of homologous recombination control in a Fanconi anemia‐like Chinese Hamster Cell mutant

Larminat

Germanier

Papouli

et al. 2004

Biology of the Cell

View full text Add to dashboard Cite

DNA interstrand cross-links (ICL)-inducing agents such as cisplatin, mitomycin C (MMC) and nitrogen mustards are widely used as potent antitumor drugs. Although ICL repair mechanism is not yet well characterized in mammalian cells, this pathway is thought to involve a sequential action of nucleotide excision repair (NER) and homologous recombination (HR). The importance of unraveling ICL repair pathways is highlighted by the hypersensitivity to ICL-inducing agents in cells of patients with the genetic disease Fanconi anemia (FA) and in cells mutated in the Breast Cancer susceptibility genes BRCA1 and BRCA2. To better characterize the involvement of HR in the sensitivity to ICL-inducing agents, we examined spontaneous and ICL-induced HR in rodent FA-like V-H4 cells. In this report, we show that MMC-hypersensitive V-H4 cells exhibit an increased spontaneous homology-directed repair (HDR) activity compared to the resistant V79 parental cells. Elevated HDR activity results mainly in increased conservative Rad51-dependent recombination, without affecting nonconservative single-strand annealing process (SSA). We also show that HDR activity is enhanced following MMC treatment in parental cells, but not in rodent FA-like V-H4 cells. Moreover, our data indicate that Rad51 foci formation is significantly delayed in these FA-like cells in response to crosslinking agent. These findings provide evidence for an impairment of HR control in V-H4 cells and emphasize the involvement of the FA pathway in HR-mediated repair.

show abstract

The Chinese hamster V79 cell mutant V-H4 is phenotypically like Fanconi anemia cells

Cited by 29 publications

References 20 publications

Interstrand Cross-Links Induce DNA Synthesis in Damaged and Undamaged Plasmids in Mammalian Cell Extracts

Interstrand Cross-Links Induce DNA Synthesis in Damaged and Undamaged Plasmids in Mammalian Cell Extracts

Different types of V(D)J recombination and end-joining defects in DNA double-strand break repair mutant mammalian cells

Impairment of homologous recombination control in a Fanconi anemia‐like Chinese Hamster Cell mutant

Contact Info

Product

Resources

About